BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:
Philadelphia chromosome-negative disease in the consolidation phase of multiphase chemotherapy ... Read More
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BLINCYTO® is indicated in adult and pediatric patients one month and older.1
*In the E1910 study, MRD was assessed centrally using standardized 6-color flow cytometry, with MRD(–) defined as < 0.01% leukemic cells in the bone marrow.2 The MRD tests were performed at laboratory sites using assays that have not been analytically validated by FDA.
ALL, acute lymphoblastic leukemia; CD, cluster of differentiation; FDA, Food and Drug Administration; MRD, measurable or minimal residual disease; Ph(–), Philadelphia chromosome–negative.
Please see Indications in above "Indications" tray and full Important Safety Information,
including BOXED WARNINGS below.
References: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen. 2. Litzow MR, Sun Z, Paietta E, et al. ECOG-ACRIN-E1910 NCTN clinical trial: A phase III randomized trial of blinatumomab for newly diagnosed BCR-ABL-negative B lineage acute lymphoblastic leukemia in adults. Presented at: 64th ASH Annual Meeting and Exposition; December 10–13, 2022; New Orleans, LA.
MT103-205, the pivotal study of BLINCYTO® in pediatric patients with R/R B-cell precursor ALL: International, open-label, single-arm, phase 1/2 study of single-agent BLINCYTO® in 70 patients < 18 years of age with B-cell precursor ALL and > 25% BM blasts who were primary refractory, in first relapse after full salvage induction, in second or later relapse, or in any relapse after HSCT. Primary endpoint was CR/CRh* in first 2 cycles: 33% (n=23/70; 95% CI: 22.1–45.1).1,2,†
Learn more about the MT103-205 pivotal study
†CR was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and full recovery of peripheral blood counts (platelets > 100,000/µL and ANC > 1,000/µL). CRh* was defined as ≤ 5% of blasts in the BM, no evidence of circulating blasts or extramedullary disease, and partial recovery of peripheral blood counts (platelets > 50,000/µL and ANC > 500/µL).1
Study design: A randomized, controlled, open-label, phase 3 study of BLINCYTO® vs chemotherapy in 111 patients 28 days to 18 years of age with high-risk,* first-relapsed, Ph(–) B-cell precursor ALL with < 25% blasts in the bone marrow after induction and 2 cycles of consolidation chemotherapy.† Patients were randomized to receive BLINCYTO®‡ or the IntReALL HR 2010 HC3 intensive combination chemotherapy§ as the third cycle of consolidation. Patients were to proceed to HSCT after this cycle of consolidation. Efficacy was established on the basis of OS and RFS. 5-year KM estimates for OS were 78.4% in the BLINCYTO® arm (n=54) vs 41.4% in the chemotherapy only arm (n=57); HR: 0.35 (95% CI: 0.17–0.70). 5-year KM estimates for RFS were 61.1% in the BLINCYTO® arm (n=54) vs 27.6% in the chemotherapy only arm (n=57); HR: 0.38 (95% CI: 0.22–0.66).1
*High risk was defined as very early or early iBM relapse, very early combined BM + EM relapse, or very early iEM relapse. Very early relapse was defined as < 18 months after primary diagnosis, and early relapse was defined as ≥ 18 months after primary diagnosis and < 6 months after completion of primary therapy.3
†Induction therapy and cycles of HC1 and HC2 chemotherapy, administered according to the IntReALL HR 2010, ALL-REZ BFM 2002, ALL R3, COOPRALL, and AIEOP ALL REC 2003 protocols.4
‡Patients in the BLINCYTO® arm received one cycle of BLINCYTO® as a continuous IV infusion at 15 mcg/m2/day over 4 weeks (maximum daily dose was not to exceed 28 mcg/day).1
§Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.3,5
OS for BLINCYTO® vs chemotherapy1
RFS for BLINCYTO® vs chemotherapy1
*Months were calculated as days from randomization
date to event/censor date, divided by 30.5.1
†The hazard ratio estimates are obtained from the Cox proportional
hazard model.1
ALL, acute lymphoblastic leukemia; ANC, absolute neutrophil count; AYA, adolescent and young adult; BM, bone marrow; CD, cluster of differentiation; CI, confidence interval; CR, complete remission; CRh*, complete remission with partial hematologic recovery; EM, extramedullary; HC1, high-risk consolidation block 1; HC2, high-risk consolidation block 2; HC3, high-risk consolidation block 3; HR, hazard ratio; HSCT, allogeneic hematopoietic stem cell transplantation; iBM, isolated bone marrow; iEM, isolated extramedullary; IM, intramuscular; IV, intravenous; KM, Kaplan-Meier; OS, overall survival; Ph(–), Philadelphia chromosome–negative; RFS, relapse-free survival; R/R, relapsed or refractory.
| Key inclusion criteria1 |
|---|
| Ph(–) B-cell precursor ALL in high-risk first relapse |
| < 25% blasts in the BM |
| Key exclusion criteria6 |
| Clinically relevant CNS pathology requiring treatment |
| Evidence of current CNS (CNS2, CNS3) involvement by ALL§ |
| Abnormal renal or hepatic function prior to start of treatment |
*High risk was defined as very early or early iBM relapse, very early combined BM + EM relapse, or very early iEM relapse. Very early relapse was defined as < 18 months after primary diagnosis, and early relapse was defined as ≥ 18 months after primary diagnosis and < 6 months after completion of primary therapy.3
†Induction therapy and cycles of HC1 and HC2 chemotherapy, administered according to the IntReALL HR 2010, ALL-REZ BFM 2002, ALL R3, COOPRALL, and AIEOP ALL REC 2003 protocols.4
‡Third block of consolidation chemotherapy, HC3, included: dexamethasone IV/vincristine IV/daunorubicin IV/methotrexate IV/ifosfamide IV/PEG-asparaginase IV/IM.3,5
§CNS2, patients with WBC count in CSF < 5 per microliter and having blasts in the CSF; CNS3, patients with WBC count in CSF ≥ 5 per microliter and having blasts in the CSF, or clinical/radiographic signs of central nervous leukemia.7
CNS, central nervous system; CSF, cerebrospinal fluid; MRD, measurable or minimal residual disease; PCR, polymerase chain reaction; WBC, white blood cell.
See the full safety profile of the Amgen 20120215 study
Learn moreStudy design: A randomized, controlled, open-label, phase 3 study of patients 1–27 years of age with Ph(–) B-cell precursor ALL in first relapse.8
*Patients who had an iBM or combined BM + EM relapse < 36 months after diagnosis or who had an iEM relapse < 18 months after diagnosis were assigned to the high-risk group.8
†Patients who had an iBM or combined BM + EM relapse ≥ 36 months after diagnosis or who had an iEM relapse ≥ 18 months after diagnosis and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.8
‡UKALLR3: induction, IT methotrexate/dexamethasone oral/mitoxantrone IV or idarubicin IV/vincristine IV/pegaspargase IM; consolidation, dexamethasone oral/vincristine IV/IT methotrexate/methotrexate IV/pegaspargase IM/cyclophosphamide IV/etoposide IV; maintenance, IT methotrexate/dexamethasone oral/vincristine IV/cytarabine IV/Erwinase IM/methotrexate IV; before HSCT, fludarabine IV/cytarabine IV/liposomal daunorubicin citrate IV.7,10
§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.8
ALL, acute lymphoblastic leukemia; BM, bone marrow; CI, confidence interval; COG, Children's Oncology Group; DFS, disease-free survival; EM, extramedullary; HR, hazard ratio; HSCT, allogeneic hematopoietic stem cell transplantation; iBM, isolated bone marrow; iEM, isolated extramedullary; IM, intramuscular; IT, intrathecal; IV, intravenous; MRD, measurable or minimal residual disease; OS, overall survival; Ph(–), Philadelphia chromosome–negative; R/R, relapsed or refractory.
IR* and HR† relapse
(HR: 0.70 [95% CI: 0.47–1.03]; P = 0.03)‡
‡The difference was not statistically significant.8
*Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months were assigned to the high-risk group.8
†Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.8
LR§ relapse
§Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction. 8
AYA, adolescent and young adult.
| Key inclusion criteria8 |
|---|
| B-cell precursor ALL in first relapse |
| Key exclusion criteria8 |
| Down syndrome |
| Ph(+) B-cell precursor ALL |
| Previous HSCT or BLINCYTO® treatment |
Baseline characteristics of patients in HR or IR first relapse8
| BLINCYTO ® (n=105) n (%) |
Chemotherapy (n=103) n (%) |
|
| Age at enrollment (years) Median (interquartile range) |
9 (6–16) | 9 (5–16) |
| 1–9 | 55 (52.4) | 55 (53.4) |
| 10–12 | 10 (9.5) | 11 (10.7) |
| 13–17 | 25 (23.8) | 19 (18.4) |
| 18–20 | 8 (7.6) | 10 (9.7) |
| 21–27 | 7 (6.7) | 8 (7.8) |
| Sex | ||
| Female | 48 (45.7) | 49 (47.6) |
| Male | 57 (54.3) | 54 (52.4) |
| Risk group assignment after reinduction | ||
| High risk* | 69 (65.7) | 69 (67.0) |
| Intermediate risk† | 36 (34.3) | 34 (33.0) |
| Cytogenetic group at diagnosis | ||
| Favorable ETV6-RUNX1, No. Hyperdiploid with +4, +10, No. |
21 (23.3) 12 9 |
16 (17.6) 8 8 |
| Unfavorable KMT2A-rearranged, No. Hypodiploid, No. |
7 (7.8) 7 0 |
10 (11.0) 9 1 |
| Other Unknown, No. |
62 (68.9) 15 |
65 (71.4) 12 |
*Patients who had an iBM or combined BM + EM relapse < 36 months or who had an iEM relapse < 18 months were assigned to the high-risk group.8
†Patients who had an iBM or combined BM + EM relapse ≥ 36 months or who had an iEM relapse ≥ 18 months and MRD ≥ 0.1% at end of induction were assigned to the intermediate-risk group.8
§UKALLR3: induction, IT methotrexate/dexamethasone oral/mitoxantrone IV or idarubicin IV/vincristine IV/pegaspargase IM; consolidation, dexamethasone oral/vincristine IV/IT methotrexate/methotrexate IV/pegaspargase IM/cyclophosphamide IV/etoposide IV; maintenance, IT methotrexate/dexamethasone oral/vincristine IV/cytarabine IV/Erwinase IM/methotrexate IV; before HSCT, fludarabine IV/cytarabine IV/liposomal daunorubicin citrate IV.7,10
‡Low risk was defined as iBM or combined BM + EM relapse ≥ 36 months or iEM relapse ≥ 18 months and MRD < 0.1% at end of induction.8
HR, high risk; IR, intermediate risk; Ph(+), Philadelphia chromosome–positive.
See the safety results of BLINCYTO® vs chemotherapy in COG AALL1331 in HR or IR first relapse
Learn moreStudy design: International, open-label, single-arm, phase 1/2 study of single-agent BLINCYTO® in patients < 18 years of age with > 25% BM blasts who were primary refractory, in first relapse after full salvage induction, in second or later relapse, or in any relapse after HSCT. Primary endpoint was CR/CRh* in first 2 cycles: 33% (n=23/70); (95% CI: 22.1–45.1).1,2
Within the First Two Treatment Cycles of BLINCYTO®
| Key inclusion criteria2 |
|---|
| Primary refractory disease |
| First relapse after full salvage induction |
| Second or later relapse, or in any relapse after HSCT |
| Age < 18 years |
| KPS ≥ 50% or LPS ≥ 50% for patients < 16 years of age |
| Key exclusion criteria2 |
| Active acute or extensive chronic GvHD after HSCT |
| Evidence of active CNS involvement |
| Evidence of active testicular involvement |
Baseline Characteristics (N=70)2,*
| Sex, n (%) | |
|---|---|
| Male | 47 (67) |
| Age, n (%) | |
| < 2 years | 10 (14) |
| 2–6 years | 20 (29) |
| 7–17 years | 40 (57) |
| Previous relapses, n (%) | |
| 0 (primary refractory disease) | 2 (3) |
| 1 | 31 (44) |
| 2 | 29 (41) |
| ≥ 3 | 8 (11) |
| Previous HSCT, n (%) | 40 (57) |
| Baseline BM blasts, n (%) | |
| < 50% | 18 (26) |
| ≥ 50% | 52 (74) |
BLAST, the pivotal study of BLINCYTO® in adult patients with MRD(+) B-cell precursor ALL: N=86, an open-label, single-arm phase 2 study of adult patients with MRD(+) B-cell precursor ALL who had received at least 3 chemotherapy blocks of standard ALL therapy, were in hematologic complete remission (defined as < 5% blasts in bone marrow, absolute neutrophil count > 1 Gi/L, platelets > 100 Gi/L), and had MRD* at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%. Primary endpoint: 81% (n=70/86) of patients had no detectable MRD assessed after 1 treatment cycle with BLINCYTO®1,12,*
*Defined as the absence of detectable MRD confirmed in an assay with minimum sensitivity of 0.01% for 6 patients and ≤ 0.005% for 80 patients. Undetectable MRD was achieved by 65 of 80 patients with an assay sensitivity of at least 0.005%.1
†Most patients (n=12) received a single 4-week course of BLINCYTO® at 15 mcg/m2/day; 2 patients had their initial cycle of BLINCYTO® shortened to start HSCT preparative therapy (at days 18 and 20), and 1 patient received 2 courses for a total of 66 days.13
‡Defined as < 5% blasts in the bone marrow.13
ALL, acute lymphoblastic leukemia; CR1, first complete remission; CR2, second complete remission; CR, complete remission; MRD, measurable or minimal residual disease; NCCN, National Comprehensive Cancer Network; R/R, relapsed or refractory.
Frontline consolidation and R/R: According to the National Comprehensive Cancer Network® (NCCN®) for Pediatric ALL recommend blinatumomab as a treatment option across lines of therapy in pediatric patients with B-cell precursor ALL with:15
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.
The incidence of signs and symptoms consistent with ICANS in clinical trials was 7.5%. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. There is limited experience with BLINCYTO® in patients with active ALL in the central nervous system (CNS) or a history of neurologic events. Patients with a history or presence of clinically relevant CNS pathology were excluded from clinical studies. Patients with Down Syndrome over the age of 10 years may have a higher risk of seizures with BLINCYTO® therapy.
Monitor patients for signs and symptoms of neurological toxicities, including ICANS, and interrupt or discontinue BLINCYTO® as outlined in the PI. Advise outpatients to contact their healthcare professional if they develop signs or symptoms of neurological toxicities.
Use the preservative-free preparations of BLINCYTO® where possible in neonates. When prescribing BLINCYTO® (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.
Monitor neonatal patients receiving BLINCYTO® (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO® 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.
BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients one month and older with:
Please see BLINCYTO® full Prescribing Information, including BOXED WARNINGS.
BLINCYTO® is a registered trademark of Amgen Inc.
References: 1. BLINCYTO® (blinatumomab) prescribing information, Amgen. 2. von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34:4381-4389. 3. Data on file, Amgen; 2020. 4. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:843-854. 5. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl 3):843-854. 6. Locatelli F, Zugmaier G, Rizzari C, et al. Effect of blinatumomab vs chemotherapy on event-free survival among children with high-risk first-relapse B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl):843-854. 7. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl 2):833-842. 8. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325:833-842. 9. Hogan LE, Brown PA, Ji L, et al. Children’s Oncology Group AALL1331: Phase III trial of blinatumomab in children, adolescents, and young adults with low-risk B-cell ALL in first relapse. J Clin Oncol. 2023. doi:10.1200/JCO.22.02200. 10. Parker C, Waters R, Leighton C, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomized trial. Lancet. 2010;376:2009-2017. 11. Brown PA, Ji L, Xu X, et al. Effect of postreinduction therapy consolidation with blinatumomab vs chemotherapy on disease-free survival in children, adolescents, and young adults with first relapse of B-cell acute lymphoblastic leukemia: a randomized clinical trial. JAMA. 2021;325(suppl):833-842. 12. Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131:1522-1531. 13. Keating AK, Gossai N, Phillips CL, et al. Reducing minimal residual disease with blinatumomab prior to HCT for pediatric patients with acute lymphoblastic leukemia. Blood Adv. 2019;3:1926-1929. 14. ClinicalTrials.gov. https://classic.clinicaltrials.gov/ct2/results?term=blinatumomab&cond=Residual+Disease%2C+Minimal&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=Intr&rslt=&Search=Apply. Accessed July 16, 2024. 15. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pediatric Acute Lymphoblastic Leukemia V.1.2025. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 3, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
